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22 pages, 1571 KB  
Systematic Review
Modulating Strategies of the Intestinal Microbiota in Colorectal Cancer
by María José García Mansilla, María Jesús Rodríguez Sojo, Andreea Roxana Lista, Ciskey Vanessa Ayala Mosqueda, Jorge García García, Julio Gálvez Peralta, Alba Rodríguez Nogales, Antonio Jesús Ruiz Malagón and María José Rodríguez Sánchez
Nutrients 2025, 17(22), 3565; https://doi.org/10.3390/nu17223565 - 14 Nov 2025
Abstract
Background/Objectives: Colorectal cancer (CRC) accounts for nearly 10% of global cancer cases and is the second leading cause of cancer-related mortality. While age and genetics are non-modifiable risk factors, nutrition and its impact on gut microbiota are emerging as key determinants in [...] Read more.
Background/Objectives: Colorectal cancer (CRC) accounts for nearly 10% of global cancer cases and is the second leading cause of cancer-related mortality. While age and genetics are non-modifiable risk factors, nutrition and its impact on gut microbiota are emerging as key determinants in CRC prevention and management. We aimed to systematically evaluate recent evidence on the role of diet and microbiota-targeted interventions—including probiotics, prebiotics, synbiotics, and postbiotics—in modulating CRC risk and therapeutic outcomes. Methods: A structured literature search was performed in PubMed, ResearchGate, Scopus, and ScienceDirect up to July of 2025. Reference lists of relevant reviews and clinical trials were also screened. A total of 36 studies were selected according to PRISMA guidelines. Data were extracted on dietary exposures, microbiota modulation, metabolite profiles, and CRC-related outcomes. Evidence quality was assessed using appropriate appraisal tools for observational and interventional designs. Results: Western-type diets were consistently associated with microbiota dysbiosis, the enrichment of pro-inflammatory and genotoxic taxa, and elevated CRC risk. Diets rich in fiber and polyphenols enhanced commensals producing short-chain fatty acids (e.g., butyrate), with anti-inflammatory and antineoplastic effects. Probiotics, prebiotics, and postbiotics demonstrated potential to restore microbial balance, improve epithelial integrity, and enhance tolerance to conventional therapies. Conclusions: Current evidence supports a complex interplay between nutrition, the gut microbiota, and CRC, with strong translational potential. Microbiota-modulating nutritional strategies, particularly fiber-rich diets and synbiotics, show the most consistent microbiota-related benefits in CRC prevention and represent promising adjuncts to standard therapies. However, much of the available research is still based on preclinical models. Therefore, there is a pressing need for well-designed clinical studies in human populations to validate these findings and inform evidence-based guidelines. Full article
(This article belongs to the Special Issue The Role of Dietary and Nutritional Factors in Cancer Treatment)
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30 pages, 12229 KB  
Article
Potential Therapeutic Effects of Epithelial and Mesenchymal Stem Cell Secretome in Benzalkonium Chloride-Induced Limbal Stem Cell Dysfunction
by Agnieszka Prusek-Kucharek, Bartosz Sikora and Piotr Czekaj
Cells 2025, 14(22), 1790; https://doi.org/10.3390/cells14221790 - 14 Nov 2025
Abstract
Dry Eye Disease (DED) is a multifactorial condition of the ocular surface, with one potential cause being damage from eye drops containing preservatives such as benzalkonium chloride (BAC). Current treatments for DED are unsatisfactory; therefore, it is worth exploring new therapies based on [...] Read more.
Dry Eye Disease (DED) is a multifactorial condition of the ocular surface, with one potential cause being damage from eye drops containing preservatives such as benzalkonium chloride (BAC). Current treatments for DED are unsatisfactory; therefore, it is worth exploring new therapies based on the secretome derived from stem cells. Human stem cells are important sources of growth factors and cytokines that promote tissue regeneration. The secretome of these cells can be obtained in vitro in conditioned medium (CM). The aim of the study was to evaluate the effect of CM derived from adipose-derived stem cells (hADSCs) and amniotic membrane-derived cells expressing mesenchymal and/or epithelial markers on limbal stem cells (LSCs) damaged by BAC, focusing on their regenerative potential. The study used two experimental models: the first focused on neutralizing the toxic effects of BAC when each CM was administered concurrently, and the second on the therapeutic effects of CM after prior cell damage by BAC. The effects of CM on LSCs were assessed, including apoptosis, cell cycle progression, proliferation, migration, and inflammation. CM from ADSCs and amniotic cells were shown to significantly reduce BAC-induced damage to LSCs. All tested CM promoted LSC regeneration, although their efficacy varied among treatments. The application of CM during BAC exposure yielded stronger and more consistent benefits than post-injury treatment. Full article
(This article belongs to the Section Cell and Gene Therapy)
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15 pages, 262 KB  
Article
Combining Natural and Microbial Insecticides with Diatomaceous Earth for Effective Management of Prostephanus truncatus
by Demeter Lorentha S. Gidari, Maria C. Boukouvala, Constantin S. Filintas, Anna Skourti and Nickolas G. Kavallieratos
Insects 2025, 16(11), 1162; https://doi.org/10.3390/insects16111162 - 14 Nov 2025
Abstract
Prostephanus truncatus is well known for causing extensive postharvest losses and threatening food security in tropical and subtropical regions. The reliance on synthetic insecticides has raised concerns about the development of resistance, environmental safety, food contamination, and human health, emphasizing the need for [...] Read more.
Prostephanus truncatus is well known for causing extensive postharvest losses and threatening food security in tropical and subtropical regions. The reliance on synthetic insecticides has raised concerns about the development of resistance, environmental safety, food contamination, and human health, emphasizing the need for alternative management strategies. Thus, the present study evaluated the insecticidal efficacy of diatomaceous earth (DE) in the Protector formula alone and in combination with spinosad, abamectin, or the entomopathogenic fungus Beauveria bassiana against P. truncatus adults and their progeny production on maize under two temperatures (25 and 30 °C) at low concentrations. Bioassays revealed that DE or B. bassiana alone induced low mortality, while spinosad and abamectin single applications resulted in high mortality rates, achieving 100% after 21 days of exposure at 30 °C at the higher concentrations. The combined applications of spinosad or abamectin with DE resulted in complete mortality and progeny suppression at lower concentrations at 25 °C. Temperature had a significant influence in some cases. Overall, these findings demonstrate that DE, when combined with other natural insecticidal agents at low concentrations, especially spinosad and abamectin at specific temperatures, can provide highly effective control of P. truncatus, offering a promising strategy for integrated pest management (IPM) in stored maize. Full article
(This article belongs to the Section Insect Pest and Vector Management)
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20 pages, 2348 KB  
Article
Effect of Fullerenol C60(OH)24 on the Viability and Metabolism of THP-1 Cells
by Darya Usanina, Svetlana Zamorina, Maria Bochkova, Valeria Timganova, Violetta Vlasova, Valeria Ponomareva, Maria Dolgikh, Sergey Lazarev and Mikhail Rayev
Molecules 2025, 30(22), 4407; https://doi.org/10.3390/molecules30224407 - 14 Nov 2025
Abstract
Fullerenols are polyhydroxylated derivatives of fullerene (C60(OH)n) with antioxidant, antiviral, and antibacterial properties and potential biomedical applications due to their solubility and biocompatibility. However, comprehensive assessment of their cytotoxicity is required, particularly regarding their effects on immune system cells. [...] Read more.
Fullerenols are polyhydroxylated derivatives of fullerene (C60(OH)n) with antioxidant, antiviral, and antibacterial properties and potential biomedical applications due to their solubility and biocompatibility. However, comprehensive assessment of their cytotoxicity is required, particularly regarding their effects on immune system cells. This study investigated the effects of fullerenol C60(OH)24 (MST-Nano, St. Petersburg, Russia) on the viability, apoptosis, and metabolism of THP-1 human monocytic leukemia cells. Cells were treated with concentrations ranging from 0.25 to 1000 µg/mL and incubated for 24, 48, and 72 h. Viability, apoptosis, and nanoparticle association were assessed by flow cytometry; glycolysis and mitochondrial respiration were measured after 24 h on a Seahorse XFe96 analyzer (Agilent Technologies, Santa Clara, CA, USA). Results showed that the effects of fullerenol depend on concentration and exposure time. At 24 h, 750 µg/mL increased viability, while 1000 µg/mL induced apoptosis. After 48 and 72 h, apoptosis increased at concentrations ≥750 µSg/mL, with reduced viability. Nanoparticle association correlated with concentration and inversely correlated with viability but was independent of incubation time. Metabolic analysis revealed decreased glycolysis at 750 µg/mL after 24 h, while mitochondrial respiration was unaffected. Thus, our study demonstrated that fullerenol nanoparticles were safe for the THP-1 monocytic cell line up to 500 µg/mL. Full article
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23 pages, 6839 KB  
Article
Source Apportionment and Potential Health Risks of Trace Metals in a Contaminated Urban River in New York/New Jersey Harbor System
by Md Shahnul Islam, Sana Mirza, Huan Feng, Tapos Kumar Chakraborty, Yu Qian and Shinjae Yoo
Water 2025, 17(22), 3254; https://doi.org/10.3390/w17223254 - 14 Nov 2025
Abstract
The Lower Passaic River (LPR), located within the New York/New Jersey Harbor Estuarine System, has experienced long-term industrial activities, resulting in elevated concentrations of trace metals in sediment and water. This study aims to assess the bioaccumulation behavior, potential human health risks, and [...] Read more.
The Lower Passaic River (LPR), located within the New York/New Jersey Harbor Estuarine System, has experienced long-term industrial activities, resulting in elevated concentrations of trace metals in sediment and water. This study aims to assess the bioaccumulation behavior, potential human health risks, and sources of copper (Cu), lead (Pb), and mercury (Hg) in the LPR. Trace metal concentrations were measured in water, sediment, and seven edible aquatic species. Data were analyzed using statistical approaches, and evaluated by bioaccumulation factors (BAFs) and human health risk assessments based on U.S. Environmental Protection Agency (USEPA) guidelines. Results showed that Hg exhibited the highest bioaccumulation potential among the studied metals, except for Cu in Callinectes sapidus. Non-carcinogenic risks from the consumption of aquatic species followed the order Cu > Hg > Pb, with total target hazard quotient (TTHQ) values below 1, suggesting the non-carcinogenic health risk is negligible for adults and for most species in children, except C. sapidus and Morone americana. Carcinogenic risks for all species were within the acceptable threshold (Target Risk < 1 × 10−4). Sensitivity analysis indicated that body weight and exposure duration primarily influenced children’s carcinogenic risk, whereas trace metal concentrations were more significant for adults. Overall, this study provides insight into contaminant dynamics and health implications in a legacy-contaminated urban river system. Full article
(This article belongs to the Section Water Quality and Contamination)
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27 pages, 9778 KB  
Article
Gut–Liver Axis Mediates the Combined Hepatointestinal Toxicity of Triclosan and Polystyrene Microplastics in Mice: Implications for Human Co-Exposure Risks
by Huijuan Liu, Jie Zhou, Zhifei Cheng, Wenhao Liu and Jiao Xie
Toxics 2025, 13(11), 977; https://doi.org/10.3390/toxics13110977 - 14 Nov 2025
Abstract
As two representative environmental contaminants, the individual toxic effects of microplastics and triclosan have been extensively studied; however, systematic evidence regarding their combined toxicity in mammals and the underlying mechanisms remains lacking. In this study, mice were orally exposed to triclosan (TCS) or/and [...] Read more.
As two representative environmental contaminants, the individual toxic effects of microplastics and triclosan have been extensively studied; however, systematic evidence regarding their combined toxicity in mammals and the underlying mechanisms remains lacking. In this study, mice were orally exposed to triclosan (TCS) or/and polystyrene microplastics (PS), and their toxicity to intestine and liver was evaluated through histopathological examination, biochemical assays, and 16S rRNA sequencing. Results demonstrated that co-exposure to TCS and PS elicited markedly aggravated toxicological effects compared to individual exposures. Histopathological evaluation revealed exacerbated tissue damage, with histological scores substantially higher in co-exposed mice (colon: 7.27; liver: 5.0) than in PS-alone (colon: 6.07; liver: 3.0) or TCS-alone (colon: 3.0; liver: 0.7) groups. Quantitative Integrated Biomarker Response (IBR) analysis confirmed this potential additive or synergistic interaction: co-exposure not only dramatically elevated colonic oxidative stress (RIB = 12.30 vs. 5.88 in PS and 0.23 in TCS groups) but also exacerbated inflammatory responses (RIB = 11.69 vs. 3.52 in PS and 0 in TCS). Hepatic assessment demonstrated the most severe compromise in liver function and oxidative homeostasis following co-exposure (RIB = 16.48), markedly exceeding the effects of individual PS (4.75) or TCS (0.43) exposure. In-depth exploration found that co-exposure to TCS and PS significantly disrupted gut microbiota homeostasis, characterized by enrichment of opportunistic pathogens and depletion of short-chain fatty acid-producing bacteria; these alterations were not only correlated with intestinal barrier impairment but also exacerbated gut–liver axis dysregulation. Together, the findings not only highlight the synergistic toxicity of triclosan and polystyrene microplastics in mice but also identify the gut–liver axis as a mediator of this effect, thereby providing novel evidence for health risk assessment and underscoring a potential concern for human health under co-exposure. Full article
(This article belongs to the Section Exposome Analysis and Risk Assessment)
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20 pages, 3294 KB  
Article
Brevetoxin Dynamics and Bioavailability from Floc Following PAC-Modified Clay Treatment of Karenia brevis Blooms
by Nicholas R. Ohnikian, Christopher D. Sibley, R. Ben Freiberger, Kristen N. Buck, Alyssa Myers, Samantha Harlow, Donald M. Anderson, Richard Pierce and Jennifer H. Toyoda
Toxins 2025, 17(11), 560; https://doi.org/10.3390/toxins17110560 - 13 Nov 2025
Abstract
Harmful algal blooms (HABs) caused by the dinoflagellate Karenia brevis present serious ecological and public health concerns due to the production of brevetoxins (BTX). Clay flocculation and sedimentation of cells, particularly with polyaluminum chloride (PAC)-modified clays, is a promising HAB mitigation approach. This [...] Read more.
Harmful algal blooms (HABs) caused by the dinoflagellate Karenia brevis present serious ecological and public health concerns due to the production of brevetoxins (BTX). Clay flocculation and sedimentation of cells, particularly with polyaluminum chloride (PAC)-modified clays, is a promising HAB mitigation approach. This study evaluated the efficacy of Modified Clay-II (MCII), a PAC-modified kaolinite clay, in reducing K. brevis cell abundance in mesocosm experiments and examined the bioavailability of BTX potentially released from settled floc back into the water column and sediment over the first 72 h after treatment. Additionally, we quantified trace metals in benthic clams (Mercenaria mercenaria) exposed to the floc post-treatment to assess metal accumulation and potential toxicological effects from MCII application. MCII treatment (0.2 g/L) resulted in a 91% reduction in K. brevis cell density and a 50% decrease in waterborne brevetoxins after 5 h. Brevetoxins accumulated in sediment post-flocculation, with BTX-B5 emerging as the dominant congener. Clams exposed to MCII-treated floc showed comparable tissue BTX levels to controls and significantly elevated aluminum concentrations, though without mortality. The aluminum accumulations in this study do not raise concerns for the health of the clams or the humans who eat them, given other dietary exposures. These findings support the potential of MCII for HAB mitigation while underscoring the need for further evaluation of exposure risks to all benthic species. Full article
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63 pages, 695 KB  
Review
Perfluoroalkyl Substances (PFAS) and Lipid Metabolism in Experimental Animal Models: A Scoping Review on the Mechanisms Behind the Induced Hepatotoxicity
by Gabriele Tancreda, Luca Campisi, Matteo Sarti, Luisa Pozzo and Andrea Vornoli
Curr. Issues Mol. Biol. 2025, 47(11), 944; https://doi.org/10.3390/cimb47110944 - 13 Nov 2025
Abstract
Per and polyfluoroalkyl substances (PFAS) are a class of synthetic, persistent environmental pollutants detected in biological systems and increasingly recognized for their harmful effects on human health. The liver, being a central organ in the metabolism of xenobiotics, is profoundly affected by these [...] Read more.
Per and polyfluoroalkyl substances (PFAS) are a class of synthetic, persistent environmental pollutants detected in biological systems and increasingly recognized for their harmful effects on human health. The liver, being a central organ in the metabolism of xenobiotics, is profoundly affected by these compounds and is a main target of PFAS-induced toxicity. The purpose of the present Scoping Review is to investigate the multiple and complex mechanisms behind PFAS hepatotoxicity, taking into consideration evidence from preclinical in vivo models. Using electronic databases (PubMed and Google Scholar), a total of 38 studies were found eligible to be extensively explored to gather information regarding PFAS toxicity toward hepatic lipid metabolism, oxidative stress, injury and inflammation. Moreover, the parental exposure of these chemicals on the offspring will be discussed as well. As illustrated in the proposed graphical abstract, PFAS exposure has been linked to the triggering of oxidative stress phenomena, mitochondrial dysfunction and hepatic inflammatory infiltrate with sex specific effects in rodents. The predominant effects manifest as the overproduction of reactive oxygen species (ROS), the disruption of hepatic lipid metabolism, and the activation of several nuclear transcription factors involved in lipid regulation, with PPAR-α being the most prominent. Considering their strong bioaccumulative properties and persistence in both the environment and the human body, legacy and emerging PFAS should be regarded as potent toxicants with a distinctive role in the onset of metabolic diseases and as a pressing issue to be addressed within regulatory policies. Full article
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20 pages, 4592 KB  
Article
Mixtures of p,p′-DDE, PCB153, BDE47, and PFOS Alter Adipocytic Differentiation of 3T3-L1 Cells
by Melanie M. Garcia, John L. Pearce, Morgan A. Jacobellis, William S. Baldwin, Kelly J. Hunt and Lisa J. Bain
Toxics 2025, 13(11), 975; https://doi.org/10.3390/toxics13110975 - 13 Nov 2025
Abstract
Exposure to certain chemicals can promote adipogenesis, but less is known about whether exposure to human-relevant chemical mixtures behaves similarly. Chemical concentrations from the serum of mothers enrolled in the Environmental Influences on Child Health Outcomes—Fetal Growth Study (n = 813) were used [...] Read more.
Exposure to certain chemicals can promote adipogenesis, but less is known about whether exposure to human-relevant chemical mixtures behaves similarly. Chemical concentrations from the serum of mothers enrolled in the Environmental Influences on Child Health Outcomes—Fetal Growth Study (n = 813) were used in a self-organizing map algorithm to identify five distinct patterns of real-world exposure mixtures containing p,p′-DDE, PCB153, BDE47, and PFOS. Each mixture profile was exposed to 3T3-L1 cells at 1×, 50×, and 500× serum levels over a 14-day adipogenic differentiation period. Cells were assessed for triglycerides and markers of adipocyte formation and maturation. The results indicate that a mixture dominated by high BDE47 levels (Profile 3) behaved differently than BDE47 alone. BDE47 alone increased expression of Fsp27, Fabp4, and Cpt1, while the Profile 3 mixture inhibited expression of these three genes. In contrast, mixtures dominated by either p,p′-DDE or PFOS (Profiles 1 and 4) behaved similarly to their dominant chemicals. Exposures inducing Pparγ increased Fsp27 levels, while those inducing Ampk reduced Fsp27 levels. These findings suggest that individual chemicals alter transcription factors that control adipogenesis, and the interplay between transcription factors yields synergistic or antagonistic chemical interactions in real-world mixture exposures. Full article
(This article belongs to the Section Exposome Analysis and Risk Assessment)
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15 pages, 2865 KB  
Article
Diverse Impact of E-Cigarette Aerosols on Oxidative Stress and Inflammation in Lung Alveolar Epithelial Cells (A549)
by Maciej Roslan, Katarzyna Milewska, Piotr Szoka, Kacper Warpechowski, Urszula Milkowska and Adam Holownia
Int. J. Mol. Sci. 2025, 26(22), 10967; https://doi.org/10.3390/ijms262210967 - 12 Nov 2025
Abstract
This study investigated the pro-inflammatory and pro-oxidative effects of popular electronic cigarette aerosols (ECAs) compared with conventional cigarette smoke (CS) in the cultured human alveolar epithelial cell line (A549). Using cytotoxicity assays and four ECAs, substantial differences in biological impact were observed. CS [...] Read more.
This study investigated the pro-inflammatory and pro-oxidative effects of popular electronic cigarette aerosols (ECAs) compared with conventional cigarette smoke (CS) in the cultured human alveolar epithelial cell line (A549). Using cytotoxicity assays and four ECAs, substantial differences in biological impact were observed. CS exposure led to significant declines in cell viability and pronounced morphological changes, consistent with the presence of toxic combustion byproducts. Most ECAs caused negligible cytotoxicity except for the tobacco-flavoured variant, which demonstrated marked toxicity. DNA damage and altered cell cycle profiles were minor. Oxidative stress analysis revealed stable superoxide dismutase activity but notable glutathione depletion, especially with watermelon- and strawberry-flavoured ECAs, and unaltered mitochondrial transmembrane potential, indicating the importance of individual flavour additives in cellular antioxidant defence. Inflammatory markers, such as TNF-α, NF-κB, and IL-6, were differentially elevated across the CS and ECA groups, with IL-6 consistently increased, underscoring its role in regulating epithelial cells. Advanced double fluorescence analysis revealed increased cellular heterogeneity and inflammation, which was distinct for all ECA flavours. Overall, the findings demonstrate considerable heterogeneity in biological effects among ECA flavourings and propose a simple ECA biomonitoring model. The results emphasise the necessity for individualised toxicity assessments, especially regarding subclinical inflammation and potential long-term health outcomes. Full article
(This article belongs to the Special Issue Molecular Research of Epithelial Function and Barrier Dysfunction)
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21 pages, 7691 KB  
Article
Physiologically Relevant Simulation of Carbohydrate Digestion: From Glycemic Index Estimation to Intestinal Cellular Responses
by Jinfeng Meng, Ying Sun, Peng Wu, Zhizhong Dong, Yuhan Qin, Liming Wang, Jie Xiao, Can Hou, Xin Ying, Jiaxing Gao, Meili Huan, Ran Chen, Yan Wang, Yufeng Wang, Jingjing Wang, Xiaodong Chen and Tai An
Foods 2025, 14(22), 3864; https://doi.org/10.3390/foods14223864 - 12 Nov 2025
Abstract
Simulating carbohydrate digestion in physiologically relevant ways remains a challenge for in vitro models. In this study, the Dynamic In vitro Human Stomach (DIVHS) system was applied to investigate cereal digestion and subsequent intestinal cellular responses. Rice, millet, and corn were digested under [...] Read more.
Simulating carbohydrate digestion in physiologically relevant ways remains a challenge for in vitro models. In this study, the Dynamic In vitro Human Stomach (DIVHS) system was applied to investigate cereal digestion and subsequent intestinal cellular responses. Rice, millet, and corn were digested under dynamic and static conditions. Compared with the static model, the dynamic system generated smaller grain fragments, a larger chyme–enzyme contact area (451.2 ± 4.4 cm2 vs. 160.4 ± 6.0 cm2), and higher average intragastric pressure (25.0 ± 1.2 kPa vs. 7.2 ± 0.7 kPa). Salivary amylase activity also declined more gradually in the dynamic system. An empirical approach for predicting the glycemic index (eGI) was proposed, which showed improved agreement with reported human GI values compared with earlier in vitro methods. Exposure of Caco-2 cells to digested products significantly altered transcriptional profiles, including protein binding, ATP binding, and glucose transporter activity. Notably, products from the dynamic model induced stronger transcriptional responses than those from the static model, including 421 genes up-regulated and 138 down-regulated. Functional enrichment highlighted pathways related to glucose transport, energy metabolism, and cellular regulation. Overall, this study demonstrates the advantages of dynamic digestion models in replicating gastrointestinal conditions, improving GI prediction, and providing mechanistic insights into intestinal cellular responses to digested carbohydrates. Full article
(This article belongs to the Section Food Nutrition)
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12 pages, 915 KB  
Review
Optimizing Oral Vitamin C Supplementation: Addressing Pharmacokinetic Challenges with Nutraceutical Formulation Approaches—A Mini Review
by Tejal Dhotre, Shefali Thanawala and Rajat Shah
Pharmaceutics 2025, 17(11), 1458; https://doi.org/10.3390/pharmaceutics17111458 - 11 Nov 2025
Viewed by 115
Abstract
Vitamin C, a water-soluble micronutrient, is one of the most widely used dietary supplements pertaining to its vital role in maintaining overall human health, particularly through its potent antioxidant and immune-supportive functions. This mini review summarizes key pharmacokinetic constraints of vitamin C and [...] Read more.
Vitamin C, a water-soluble micronutrient, is one of the most widely used dietary supplements pertaining to its vital role in maintaining overall human health, particularly through its potent antioxidant and immune-supportive functions. This mini review summarizes key pharmacokinetic constraints of vitamin C and evaluates formulation strategies aimed at improving its systemic availability. Achieving sustained optimal plasma levels of vitamin C remains challenging due to its dose-dependent absorption, tissue saturation, rapid renal clearance, and short half-life. These pharmacokinetic limitations restrict systemic retention, with high oral doses providing only marginal increases in plasma concentrations and necessitating multiple daily administrations. Conventional vitamin C supplements show efficient absorption only at low to moderate doses, while higher intakes are restricted by transporter saturation and increased renal excretion. Alternative delivery systems such as liposomal encapsulation, esterified derivatives, nano-emulsions, and co-formulations with bioenhancers have been examined; however, evidence for prolonged systemic retention remains inconsistent. The sustained-release formulation of vitamin C shows more reliable outcomes, demonstrating prolonged plasma exposure, higher steady-state concentrations, and potential for improved compliance through reduced dosing frequency. While further robust comparative studies are needed, current evidence suggest that advanced formulation approaches, particularly sustained-release delivery, may help overcome these pharmacokinetic limitations, thereby supporting improved clinical utility of vitamin C supplementation. Full article
(This article belongs to the Special Issue Methods of Potentially Improving Drug Permeation and Bioavailability)
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15 pages, 2758 KB  
Article
Altered Transcriptome Signature in Primary Human Myotubes Exposed to Inclusion Body Myositis Serum: A Pilot Case Comparison of Anti-cN1A Positive and Negative Sera
by Nataliya Slater, Abha Chopra, Ramesh Ram, Abbie Adams, Frank L. Mastaglia, Merrilee Needham and Jerome D. Coudert
Muscles 2025, 4(4), 53; https://doi.org/10.3390/muscles4040053 - 10 Nov 2025
Viewed by 111
Abstract
Inclusion body myositis (IBM) is a late-onset, treatment-resistant inflammatory myopathy. Approximately half of IBM patients develop autoantibodies against cytosolic 5-nucleotidase 1A (cN1A), but their role in disease pathogenesis remains unclear. This pilot study examined the effects of anti-cN1A-positive IBM serum on [...] Read more.
Inclusion body myositis (IBM) is a late-onset, treatment-resistant inflammatory myopathy. Approximately half of IBM patients develop autoantibodies against cytosolic 5-nucleotidase 1A (cN1A), but their role in disease pathogenesis remains unclear. This pilot study examined the effects of anti-cN1A-positive IBM serum on human primary myotubes’ transcriptome profile, using anti-cN1A-negative IBM and healthy sera as controls. Exposure to anti-cN1A-positive serum altered the expression of 1126 genes, with upregulation of adaptive immune response genes, notably CTSH and CTSZ, encoding cathepsins H and Z. These findings were validated using a publicly available independent dataset comprising transcriptomes from fresh muscle tissue samples. NT5C1A mRNA, which encodes cN1A, was not detected in cultured myotubes regardless of the presence of autoantibodies. The findings suggest distinct pathological mechanisms in anti-cN1A-positive IBM, independent of direct antibody-target interactions. The role of cathepsins in IBM pathogenesis warrants further investigation. Full article
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26 pages, 2178 KB  
Article
Air Sensor Network Analysis Tool: R-Shiny Application
by Karoline K. Barkjohn, Todd Plessel, Jiacheng Yang, Gavendra Pandey, Yadong Xu, Stephen Krabbe, Catherine Seppanen, Renée Bichler, Huy Nguyen Quang Tran, Saravanan Arunachalam and Andrea L. Clements
Atmosphere 2025, 16(11), 1270; https://doi.org/10.3390/atmos16111270 - 8 Nov 2025
Viewed by 322
Abstract
Poor air quality can harm human health and the environment. Air quality data are needed to understand and reduce exposure to air pollution. Air sensor data can supplement national air monitoring data, allowing for a better understanding of localized air quality and trends. [...] Read more.
Poor air quality can harm human health and the environment. Air quality data are needed to understand and reduce exposure to air pollution. Air sensor data can supplement national air monitoring data, allowing for a better understanding of localized air quality and trends. However, these sensors can have limitations, biases, and inaccuracies that must first be controlled to generate data of adequate quality, and analyzing sensor data often requires extensive data analysis. To address these issues, an R-Shiny application has been developed to assist air quality professionals in (1) understanding air sensor data quality through comparison with nearby ambient air reference monitors, (2) applying basic quality assurance and quality control, and (3) understanding local air quality conditions. This tool provides agencies with the ability to more quickly analyze and utilize air sensor data for a variety of purposes while increasing the reproducibility of analyses. While more in-depth custom analysis may still be needed for some sensor types (e.g., advanced correction methods), this tool provides an easy starting place for analysis. This paper highlights two case studies using the tool to explore PM2.5 sensor performance under the conditions of wildfire smoke impacts in the Midwestern United States and the performance of O3 sensors for a year. Full article
(This article belongs to the Special Issue Emerging Technologies for Observation of Air Pollution (2nd Edition))
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13 pages, 493 KB  
Article
Sustainable Management Practices to Include Mixtures of Chemicals in Regulatory Approaches Focusing on the Global South
by Vitor Pereira Vaz, David Dewez, Philippe Juneau, William Gerson Matias and Maria Elisa Magri
Sustainability 2025, 17(22), 9976; https://doi.org/10.3390/su17229976 - 8 Nov 2025
Viewed by 185
Abstract
Environmental pollution is becoming increasingly unpredictable over time due to its complexity, given the number of new chemicals produced annually and the constantly changing environmental conditions. Regulation has yet to keep pace with the rapid changes posed by chemical mixtures, especially in the [...] Read more.
Environmental pollution is becoming increasingly unpredictable over time due to its complexity, given the number of new chemicals produced annually and the constantly changing environmental conditions. Regulation has yet to keep pace with the rapid changes posed by chemical mixtures, especially in the Global South. Understanding the potential outcomes of co-exposure to multiple compounds can be challenging, even for professionals with a background in sustainability and mixture toxicity, due to the complexity of the issue. Some tools have been developed to tackle this uncertainty like the Species Sensitivity Distribution curve (SSD), the Adverse Outcome Pathways (AOP), and the Mixture Assessment Factor (MAF). This study aims to bridge the gap between knowledge generated in the field of mixture toxicity and regulatory practices by proposing sustainable management practices at the local scale, particularly for countries in the Global South. The proposed framework is called GlORIES and comprises the following measures. The first proposed step is to describe the chemicals used in industries or identified in existing environmental studies and/or monitoring campaigns on a watershed basis. Having a watchlist of compounds and organisms present in the region, and by generating a regionalized SSD, it is possible to use models such as AOPs to try to predict which compounds could potentially interact and thus generate a correcting factor, such as a MAF. A MAF could then be incorporated into regulations to further protect the environment by reducing the concentration of the compound in the mixture. Including local communities in reporting human and environmental health alterations could be a key to identifying the possible harmful emissions. It is proposed that watershed management committees be established to integrate all stakeholders and promote workshops organized by academia, industry, regulatory agencies, and civil society, leveraging existing structures to conserve energy in the process. The proposed framework can improve the sustainability of the process and the knowledge flow from academia to regulatory bodies, increasing the efficacy of the chosen water quality thresholds by adapting to real-life scenarios. Full article
(This article belongs to the Section Sustainable Management)
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